Unraveling the intricate organization of mammalian mitochondrial presequence translocases: existence of multiple translocases for maintenance of mitochondrial function

Mol Cell Biol. 2014 May;34(10):1757-75. doi: 10.1128/MCB.01527-13. Epub 2014 Mar 17.

Abstract

Mitochondria are indispensable organelles implicated in multiple aspects of cellular processes, including tumorigenesis. Heat shock proteins play a critical regulatory role in accurately delivering the nucleus-encoded proteins through membrane-bound presequence translocase (Tim23 complex) machinery. Although altered expression of mammalian presequence translocase components had been previously associated with malignant phenotypes, the overall organization of Tim23 complexes is still unsolved. In this report, we show the existence of three distinct Tim23 complexes, namely, B1, B2, and A, involved in the maintenance of normal mitochondrial function. Our data highlight the importance of Magmas as a regulator of translocase function and in dynamically recruiting the J-proteins DnaJC19 and DnaJC15 to individual translocases. The basic housekeeping function involves translocases B1 and B2 composed of Tim17b isoforms along with DnaJC19, whereas translocase A is nonessential and has a central role in oncogenesis. Translocase B, having a normal import rate, is essential for constitutive mitochondrial functions such as maintenance of electron transport chain complex activity, organellar morphology, iron-sulfur cluster protein biogenesis, and mitochondrial DNA. In contrast, translocase A, though dispensable for housekeeping functions with a comparatively lower import rate, plays a specific role in translocating oncoproteins lacking presequence, leading to reprogrammed mitochondrial functions and hence establishing a possible link between the TIM23 complex and tumorigenicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Proliferation
  • DNA Copy Number Variations
  • DNA, Mitochondrial / genetics
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • MCF-7 Cells
  • Mitochondria / enzymology*
  • Mitochondria / genetics
  • Mitochondrial Membrane Transport Proteins / metabolism*
  • Mitochondrial Membranes / enzymology*
  • Mitochondrial Proteins / metabolism
  • Protein Subunits / metabolism
  • Protein Transport

Substances

  • DNA, Mitochondrial
  • Mitochondrial Membrane Transport Proteins
  • Mitochondrial Proteins
  • Protein Subunits
  • TIMM23 protein, human
  • Tim17 protein, human
  • magmas protein, human